Our prior work supportedthe validity of a new animal model of endogenous depression. Rats treatedneonatally with cloimipramine (CLI) developed a delayed adult "depression" with behavioral abnormalities, REM sleep abnormalities, and treatment responses similar to those of endogenous depression. Recent work indicates that other antidepressant drugs, administered neonatally to rats, also produce adult depressive behaviors. The goal of the proposed work is to shed light on brain processes involved in the cause and improvement of the animal "depression". The first is that administered to neonatal rats, antidepressant drugs result in a long term down-regulation of amine receptors (5HT2 and beta adrenergic) and/or diminution of aminergic nerve impulses in noradrenergic (NA) neurons of the locus coeruleus and serotonergic (5HT) neurons of the dorsal raphe nucleus. The animals are then deprived of behavioral stimulation provided by monoamines and become depressed. Our specific aims are to test this hypothesis by determining whether several antidepressant drugs, administered to neonatal rats have a common lowering effect on the above amine receptors in neonates or in adult "depressed" rats and also decrease aminergic nerve impulses in the adult. Such a common effect of different causes of depression would be a likely pathway that mediates the depression. The second hypothesis about pathogenesis is that the antidepressant drugs cause the later depression by neonatal REM sleep deprivation (RSD) without a REM rebound. All antidepressant drugs whose neonatal administration causes later depressive behaviors produce neonatal RSD without immediate REM rebound. Our specific aim is to thest theis hypothesis by detgermining whether (1) normalizing REM sleep levels in CLI treated neonatal rats will prevent the later depresnormalizing REM sleep levels in CLI treated neonatal rats will prevent the later depression; and (2) inducing a neonatal REM rebound immediately after CLI will prevent the later depression. As mentioned, another long term goal of the work is to investigate brain processes that mediate the improvement of the depression. Our specific aim is to test the hypothesis that in adult "depressed" rats several efficacious antidepressant treatments have a common effect on amine receptors or aminergic neuronal impulses. Again, such a common effect of different treatmentswould bea likely mediatorof improvement.A positive finding in the proposed work would producea powerful tool for future research and may shedlight on the causes and treatment of endogenous depression.